Growth-Promoting Effect of Growth Hormone and Low Dose Ethinyl Estradiol in Girls with Turner's Syndrome*

Vanderschueren-Lodeweyckx, M; Maes, Marc; Massa, Guy; Craen, Margarita; Vanvliet, G.; Heinrichs, Claudine; Malvaux, P

doi:10.1210/jcem-70-1-122

Cited by 72 publications

(34 citation statements)

References 17 publications

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“…Since the successful synthesis of hGH by recombinant DNA technology (6), several investigators have reported the safety and biological activity of recombinant hGH (rhGH) in humans. hGH therapy in Turner's syndrome began systematically several years ago as clinical trials (7)(8)(9)(10)(11). Although GH could obviously induce a substantial increase in the rate of increase in height, the long-term outcome in terms of final height is still unclear.…”

Section: Introductionmentioning

confidence: 99%

Clinical trials of GH treatment in patients with Turner's syndrome in Japan--a consideration of final height. The Committee for the Treatment of Turner's Syndrome

Takano

Ogawa

Tanaka

et al. 1997

European Journal of Endocrinology

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Clinical trials of human GH (hGH) therapy in Turner's syndrome were started in 1986. Between 1986 and 1990, 362 patients were enrolled; 115 were treated for more than 6 years. The age at the start of treatment ranged from 5 to 18 years (mean 10 years). Fifty-one patients received hGH at a weekly dosage of 0.5 IU/kg and 64 received 1.0 IU/kg by daily s.c. injection. Both treatment groups showed a statistically significant growth increase during the initial 4 years of treatment. The rate of increase in height was significantly greater for the initial 2 years with the high dose than with the low dose. The increases in height over 6 years of treatment (expressed by S.D. score for chronological age) were 1.48 Ϯ 0.8 with 0.5 IU/kg per week and 1.80 Ϯ 1.0 with 1.0 IU/kg per week. To date, 260 patients have stopped GH therapy. In 32% of them, the height attained was above the ¹2 S.D. value for normal girls. In 27%, the growth rate was not sufficient when they stopped treatment. The mean final height (growth rate Յ1.0 cm/year) of patients treated for more than 6 years was 142.2 Ϯ 6.5 cm (n ¼ 15) with 0.5 IU/kg per week, and 144.3 Ϯ 3.9 cm (n ¼ 15) with 1.0 IU/kg per week. The adult height was improved by GH treatment, although final height did not differ statistically between the two dose regimens. No remarkable adverse events occurred during the treatment. These results indicate that hGH treatment improves the final height in patients with Turner's syndrome.

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Section: Introductionmentioning

confidence: 99%

Clinical trials of GH treatment in patients with Turner's syndrome in Japan--a consideration of final height. The Committee for the Treatment of Turner's Syndrome

Takano

Ogawa

Tanaka

et al. 1997

European Journal of Endocrinology

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“…The plasma estradiol level corresponding to this dose is -4 pg/ml based on extrapolation from the levels at higher dose infusions. Additionally, ethinyl estradiol doses as low as 25-100 ng/kg per day cause increased growth velocity in girls with Turner syndrome (4)(5)(6).…”

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confidence: 99%

Estrogen levels in childhood determined by an ultrasensitive recombinant cell bioassay.

Klein¹,

Baron²,

Colli³

et al. 1994

J. Clin. Invest.

351

224

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We hypothesized that estradiol levels are higher in prepubertal girls than in prepubertal boys and that this greater secretion of estradiol might drive the more rapid epiphyseal development and earlier puberty in girls. Since previous estradiol assays have lacked adequate sensitivity to test the hypothesis of higher estradiol levels in girls, we developed a new ultrasensitive assay to measure estrogen levels. The assay uses a strain of Saccharomyces cerevisiae genetically engineered for extreme sensitivity to estrogen. Yeast were transformed with plasmids encoding the human estrogen receptor and an estrogen-responsive promoter fused to the structural gene for f-galactosidase. Ether extracts of 0.8 ml of serum were incubated with yeast for 8 h and the 38-galactosidase response was used to determine estrogen bioactivity relative to estradiol standards prepared in charcoalstripped plasma. The assay was highly specific for estradiol with < 3 % cross-reactivity with estrone, estriol, or estradiol metabolites. The detection limit was < 0.02 pg/ml estradiol equivalents (100-fold lower than existing assays). Using this assay, we measured estrogen levels in 23 prepubertal boys (9.4±2.0 yr) and 21 prepubertal girls (7.7+1.9 [SD] yr). The estrogen level in girls, 0.6+0.6 pg/ml estradiol equivalents, was significantly greater than the level in boys, 0.08+0.2 pg/ml estradiol equivalents (P < 0.05). We conclude that the ultrasensitive recombinant cell bioassay for estrogen is approximately 100-fold more sensitive than previous estradiol assays, that estrogen levels are much lower prepubertally, in both sexes, than reported previously, and that prepubertal girls have 8-fold higher estrogen levels than prepubertal boys. (J. Clin. Invest. 1994Invest. . 94:2475Invest. -2480

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“…Recently, many trials with r-hGH have shown that supraphysiologic doses of the hormone increase the height velocity of these girls (1)(2)(3)(4), permitting them to grow beyond their genetic potential (5). However, the pathogenesis of the growth disorder remains to be elucidated so far.…”

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confidence: 99%

Plasma Growth Hormone-Binding Protein Activity, Insulin-like Growth Factor I, and Its Binding Protein Levels in Patients with Turner's Syndrome: Effect of Short- and Long-Term Recombinant Human Growth Hormone Administration

1995

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Plasma growth hormone-binding protein (GH-BP) activity and the levels of IGF-I and its binding proteins (IGFBP) were studied in eight girls with Turner's syndrome before and during recombinanthGH (r-hGH) administration. Growth hormone and GH-BP activity were assayed at baseline and hourly, over a 12-h period, after an intramuscular bolus of 0.09 mgikg of the hormone. After 7 d, each patient received r-hGH at 0.33 mgikg/weekly s.c. every day at nighttime; plasma growth hormone-binding protein activity, blood IGF-I, and IGFBP were evaluated before and on d 7, 30, 180, and 360. Baseline reference values were obtained from 10 bone agematched healthy girls. Basal GH-BP activity, IGF-I, and IGFBP levels were similar in patients and controls. Four h after the intramuscular injection, GH-BP activity maximally increased and returned to baseline 6-7 h later; during long-term r-hGH administration GH-BP activity peaked at + 180 d but declined to pretreatment at +360 d. IGF-I, IGFBP-3, and IGFBP-4 increased under r-hGH and, in contrast to GH-BP activity, remained high throughout the study. In conclusion, in girls with Turner's syndrome, GH-BP activity, IGF-I, IGFBP-3, and IGFBP-4 are induced by r-hGH. However, the increase of IGF-I and IGFBP-3 does not require an increased level of the cellular growth hormone receptors, as suggested by the unchanged +360 d values of plasma GH-BP activity compared with baseline. The absence of an association among any of the biochemical parameters studied and the growth of the patients taking r-hGH suggests that a peripheral defect may affect their growth. (Pediatr Res 37: 106111, 1995)

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Growth-Promoting Effect of Growth Hormone and Low Dose Ethinyl Estradiol in Girls with Turner's Syndrome*

Cited by 72 publications

References 17 publications

Clinical trials of GH treatment in patients with Turner's syndrome in Japan--a consideration of final height. The Committee for the Treatment of Turner's Syndrome

Clinical trials of GH treatment in patients with Turner's syndrome in Japan--a consideration of final height. The Committee for the Treatment of Turner's Syndrome

Estrogen levels in childhood determined by an ultrasensitive recombinant cell bioassay.

Plasma Growth Hormone-Binding Protein Activity, Insulin-like Growth Factor I, and Its Binding Protein Levels in Patients with Turner's Syndrome: Effect of Short- and Long-Term Recombinant Human Growth Hormone Administration

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